What Is Known/What Is New
What Is Known
- Despite standard treatment, a significant portion of pediatric patients with Crohn's disease have persistent abdominal pain, psychosocial impairment, and reduced quality of life compared with healthy peers.
- Clinical hypnosis is an effective and low-risk therapy for abdominal pain and psychological distress.
What Is New
- Clinical hypnosis is a feasible and acceptable adjunct to standard care in adolescents with Crohn's disease.
- Clinical hypnosis may improve pain and psychosocial well-being in these patients.
Crohn's disease (CD), a type of inflammatory bowel disease (IBD) increasingly prevalent in youth (1), is a chronic, immune-mediated condition associated with abdominal pain, altered bowel habits, fatigue, and delayed growth. Over a quarter of pediatric patients may continue to have pain even during disease remission (2). Mood and anxiety disorders are more common in patients with childhood-onset IBD compared with the general population, with reported hazard ratios of 1.6 and 1.9, respectively (3), whereas access to mental healthcare is often limited (4). School performance and social functioning may be impaired by factors including embarrassing bowel symptoms and an unpredictable disease course (5,6), whereas disruptive nocturnal symptoms and cytokine effects may lead to poor sleep (7). Pain, psychosocial dysfunction, and other symptoms that persist despite usual treatment often impair quality of life (QoL) for these patients, many of whom seek complementary therapies to alleviate these symptoms (8,9).
Clinical hypnosis (CH) involves inducing a relaxed and focused state followed by therapeutic suggestions to create desired physiologic and psychologic change (10). Children and adolescents are excellent candidates for hypnosis by virtue of their vivid imaginations (10). Randomized controlled trials (RCTs) demonstrate the efficacy of hypnosis for functional abdominal pain (FAP) in adults, including those with refractory symptoms (11), and in children, with benefits enduring at 5-year follow-up (12). CH is also beneficial for other types of chronic pain (13), anxiety (14), sleep (15), and as an adjunct to cognitive behavioral therapy (CBT) for depression (16). Used alongside medical procedures and surgeries, CH can reduce pain, distress, and healthcare costs (17–19). CH may also help control inflammation by modulating neuroimmune pathways altered in both chronic stress and IBD (20,21) by way of vagal nerve stimulation (22) and reduction of pro-inflammatory cytokines (23,24).
A biopsychosocial approach may benefit patients with CD, in whom psychological factors influence symptom perception and reporting (25), and may alter disease course (21). Given risks associated with nonsteroidal anti-inflammatory drugs and opiates, and suboptimal access to psychotherapy, novel options for pain control are needed (4,26). CH has no significant adverse effects (13). To date, there are no RCTs of CH in CD or in pediatric patients with IBD, but there is strong conceptual support for its value.
We aimed to implement a CH intervention consisting of a single in-person session followed by 8 weeks of self-hypnosis practice at home, as an adjunct to standard care in adolescents with CD. We hypothesized that patients receiving CH would experience significant improvement from baseline to postintervention and compared with a control group in QoL, pain, psychological distress, and school attendance using patient and parent-reported measures, and in disease activity measures.
The study was approved by the Vanderbilt University Institutional Review Board and registered with ClinicalTrials.gov registry number NCT03809195.
Forty patients were recruited from the Pediatric Gastroenterology (GI) Division at a tertiary regional academic medical center. Patients were primarily recruited in the outpatient setting; inpatients on the pediatric GI service were also eligible. Criteria for inclusion were ages 12 to 18 years old; formal CD diagnosis at least 3 months before enrollment; inactive to moderate disease activity by Physician's Global Assessment (PGA); cognitive capacity to listen to CH sessions and complete surveys; and having an electronic device on which to listen to audio files, receive text messages, and complete online surveys.
Patients were approached and informed about CH and its possible benefits for IBD. They were offered modest monetary compensation for participation. Informed consent/assent was obtained from parents and patients. Patients were randomized one-to-one to a hypnosis intervention group (HI) or a waitlist control group (WC), stratified by sex and disease activity (inactive/mild vs moderate by PGA), using the randomization tool generator with randomly permuted blocks of 2 on randomization.com. WC patients could participate in CH after the study period.
Following randomization, each patient and 1 parent/caregiver completed a series of patient-reported outcome measures. Study data were collected and managed using REDCap (Research Electronic Data Capture), a secure, web-based database (27). Patients were then interviewed regarding symptoms, mood, and interests. Those randomized to HI underwent 1 CH session described below. Data were collected from patients via online surveys weekly for 8 weeks and at 16 weeks postintervention, and from parents at weeks 8 and 16. Links to surveys were sent via automated text message to patients and e-mail to parents. Study flowchart is depicted in Supplemental Figure 1, https://links.lww.com/MPG/C21. Author A.L. enrolled and randomized patients and delivered the intervention.
After the interview, HI patients underwent an in-person, scripted, 25-minute CH session that involved an induction focused on relaxation and a range of suggestions targeting comfort, calm, and strength. Minor components of the session were individualized based on the interview. Patients were then instructed in methods of self-hypnosis with and without audio recordings (28) and were provided 4 recordings for continued use, with instructions to practice each daily for 1 week, then at their discretion. HI patients received 8 weeks of daily text message reminders to practice, then were not contacted again until week 16.
Demographic data including age; sex; parental education; expectancies regarding CH; and disease behavior, location, activity, time of diagnosis, and therapy were extracted from the medical record and surveys.
At baseline, week 8, and week 16, patients and parents completed a compilation of survey measures; patients also completed brief weekly surveys on weeks 1 through 7. The primary outcome was change in QoL from baseline to week 8. Secondary outcomes included change in abdominal pain, depressive symptoms, anxiety, sleep disturbance, and school absences from baseline to weeks 8 and 16, QoL at week 16, and disease activity at routine follow-up.
Patient-reported measures included the Impact III (29); modified Cantril scale (30) (MCS); 3 items from the Abdominal Pain Index (31) (API); and Patient-Reported Outcomes Measurement Information System (PROMIS) Pediatric Short Form v2.0—Anxiety 8a (32), Pediatric Short Form v2.0—Depressive Symptoms 8a (32), and Pediatric Short Form v1.0—Sleep Disturbance 8a (33,34). Parent-reported measures included the Pediatric Quality of Life Inventory (35) (PedsQL) v4.0 Generic Core Scale Parent-Proxy and number of school absences for the child in the past 8 weeks. HI patients also reported self-hypnosis practice frequency and provided qualitative feedback (see Suppl Fig. 1, https://links.lww.com/MPG/C21). Assessment of disease activity was based on the Pediatric Crohn's Disease Activity Index (PCDAI) and fecal calprotectin.
The Impact III measures pediatric IBD-specific health-related quality of life (HRQoL) with total and 6 subdomain scores: bowel symptoms, emotional functioning, social functioning, systemic symptoms, body image, and treatment/interventions. PedsQL measures HRQoL with total and 4 subdomain scores: physical, emotional, social, and school functioning. The MCS is a single-item QoL measure. Higher scores on QoL measures indicate better QoL. Higher scores on PROMIS measures represent higher levels of the construct (eg, greater anxiety). On the API, patients rate maximum and usual pain severity from 0 to 10 and pain frequency from 0 (never) to 4 (daily).
Forty patients allowed for 80% power to detect a 13-point difference in Impact III scores, an approximation of clinically meaningful differences between active and inactive IBD (29,36,37). Robust, permutation-based t-tests were used to compare within-individual changes over time (paired tests) and between-group changes from baseline to follow-up (HI vs WC; independent tests). Mean differences for within-group and between-group changes were estimated with bootstrap confidence intervals (38). A 2-sided significance level of 0.05 was used. All results are reported without formal adjustment for multiple comparisons. Analyses by randomization group were intent-to-treat.
Forty patients were enrolled February through May 2019. The study period ended in September 2019. Sixty-five percent of patients approached enrolled in the study. Thirty-six outpatients and 1 inpatient were recruited, and 3 patients self-referred. Patients declined primarily because of time conflicts. Notably, none cited concerns related to misconceptions about hypnosis, such as loss of control. See Supplemental Figure 1, https://links.lww.com/MPG/C21.
Baseline surveys were completed by all participants except 1 HI parent. Most baseline demographics were similar between the 2 groups, though on some measures, WC scores reflected significantly poorer functioning compared with HI (Table 1).
TABLE 1 -
Baseline demographics and scores for hypnosis intervention and waitlist control patients, reported as mean ± standard deviation or number and percent of total, with P
values for difference between groups
||HI (n = 20)
||WC (n = 20)
|Female, n (%)
|Age in years
||15.5 ± 2
||16.1 ± 2
|Inactive disease, n (%)
|Mild disease, n (%)
|Moderate disease, n (%)
||7.9 ± 7.1
||11.4 ± 9.5
|Biologic therapy, n (%)
||73.7 ± 15.6
||65.3 ± 14.4
|Impact bowel symptoms
||73.6 ± 18.5
||68.4 ± 18.7
||70 ± 18
||58.1 ± 20.9
||78.2 ± 14.4
||72.8 ± 17.5
|Impact systemic symptoms
||66.3 ± 27.6
||45.4 ± 20.1
|Impact body image
||68.1 ± 23.9
||55.4 ± 20.6
||76.7 ± 16.3
||75 ± 16.5
||76.2 ± 14.1
||69 ± 14.9
||80.1 ± 15.8
||70 ± 22
||70.8 ± 18.4
||62.8 ± 18.2
||82.9 ± 19.2
||77.5 ± 16.5
||68.7 ± 19.4
||65 ± 16.6
||7.1 ± 2.2
||6.1 ± 2
|Persistent pain, n (%)
|Usual abdominal pain
||2.7 ± 2.6
||2.5 ± 2.3
|Most abdominal pain
||3.3 ± 2.9
||2.8 ± 2.8
|Abdominal pain Frequency
||0.9 ± 1.1
||1.3 ± 1.4
||46.9 ± 12.5
||56.7 ± 12
||45.2 ± 9.7
||49.6 ± 11
||50.1 ± 12.1
||57.5 ± 10.1
|School absences, days
||4.7 ± 3.9
||3.5 ± 3.4
HI = hypnosis intervention; MCS = Modified Cantril Scale; PCDAI = Pediatric Crohn's Disease Activity Index; PedsQL = Pediatric Quality of Life Inventory; WC = waitlist control.
Week 8 surveys were completed by 17/20 HI patients, 17/19 HI parents, 20/20 WC patients, and 14/20 WC parents.
Patient-reported QoL, within-group findings: in HI, there were no significant differences in Impact III or MCS from baseline to week 8. In WC, the only significant difference was improvement in the Impact III systemic symptom subdomain, which at baseline was significantly lower than HI and scores reported in the literature (37).
Patient-reported QoL, between-group findings: there were no significant between-group differences in Impact III or MCS from baseline to week 8.
Parent-reported QoL, within-group findings: In HI PedsQL scores improved significantly in total score and the emotional, social, and school functioning subdomains from baseline to week 8. In WC, no significant differences were seen in PedsQL total or subdomain scores. Findings are depicted in Fig. 1.
Parent-reported QoL, between-group findings: PedsQL scores improved significantly more in HI than in WC in total score, social functioning, and school functioning.
Primary outcomes are detailed in Table 2.
TABLE 2 -
Mean differences and 95% confidence intervals within each group from baseline to week 8 and between groups for primary and secondary outcome measures
||HI, 0 to 8 weeks
||WC, 0 to 8 weeks
||HI-WC between groups
||MD [95% CI]
||MD [95% CI]
||MD [95% CI]
| Impact total
||3.2 [−4.1 to 10.2]
||1.5 [−1.6 to 4.4]
||1.7 [−6.1 to 9.4]
| Impact bowel symptoms
||0.01 [−10.1 to 9.7]
||−1.8 [−11.7 to 3.9]
||1.8 [−9.5 to 15.1]
| Impact social
||2.5 [−2.9 to 7.9]
||−0.3 [−3.6 to 3.3]
||2.8 [−4.1 to 8.8]
| Impact emotional
||8.2 [0.2 to 16.6]
||5.1 [0.3 to 11.2]
||3.1 [−6.8 to 12.3]
| Impact systemic symptoms
||3.9 [−9.3 to 18.2]
||8.3 [1.7 to 15.8]
||−4.4 [−18.7 to 12.4]
| Impact body image
||2.2 [−5.9 to 9.3]
||2.9 [−4.2 to 9.2]
||−0.7 [−10.6 to 9.4]
| Impact treatments
||2.9 [−5.4 to 10.8]
||−2.6 [−11.5 to 4.2]
||5.5 [−5.7 to 16.6]
| PedsQL Total
||7.7 [3.5 to 13]
||−0.9 [−7.8 to 6.2]
||8.7 [0.4 to 17.6]
| PedsQL Physical
||4.8 [−1.1 to 10.3]
||−2.2 [−14.7 to 6.5]
||7 [−3.4 to 20.2]
| PedsQL Emotional
||6.5 [0.3 to 12.1]
||1.8 [−7.5 to 7.5]
||4.7 [−3.6 to 15.4]
| PedsQL Social
||7.4 [2.9 to 15]
||−3.6 [−9.6 to 2.9]
||10.9 [2.9 to 20.1]
| PedsQL School
||14.1 [7.1 to 23.2]
||1.1 [−7.5 to 11.4]
||13 [0.9 to 25.7]
||0.7 [−0.5 to 1.4]
||0.7 [−0.4 to 1.8]
||0.1 [−1.5 to 1.3]
| Usual abdominal pain
||−1.1 [−2.2 to −0.1]
||0.0 [−1.1 to 1]
||−1.1 [−2.5 to 0.3]
| Most abdominal pain
||−1.4 [−2.4 to −0.6]
||0.3 [−0.7 to 1.7]
||−1.7 [−3.2 to −0.3]
| Abdominal pain frequency
||−0.2 [−0.8 to 0.3]
||0.2 [−0.3 to 0.6]
||−0.3 [−1.1 to 0.4]
| Depressive symptoms
||0.5 [−4.3 to 6]
||−1.6 [−4.8 to 1.5]
||2.1 [−3.5 to 8.4]
||−1.4 [−5.9 to 5.5]
||−0.5 [−3.7 to 2.7]
||−0.9 [−6.3 to 6.5]
| Sleep disturbance
||−0.5 [−7.4 to 4.8]
||−3.3 [−6.8 to 0]
||2.8 [−5 to 9.1]
| School absences
||−2.5 [−4.5 to −0.9]
||−0.8 [−4.1 to −0.1]
||−1.7 [–3.6 to 0.7]
||2 [−1.5 to 8.2]
||0.3 [−4.5 to 4.3]
||1.7 [−4 to 8.7]
HI = hypnosis intervention; MCS = Modified Cantril Scale; PCDAI = Pediatric Crohn's Disease Activity Index; PedsQL = Pediatric Quality of Life Inventory; WC = waitlist control.
Baseline to week 8: in HI, patients had significant improvement in both usual and most abdominal pain severity and greater improvement in most pain compared with WC, whereas WC patients had no significant improvement in abdominal pain measures (Fig. 2). School absences decreased in 59% of HI patients compared with 14% in the WC group (P = 0.01, Supplemental Fig. 2, https://links.lww.com/MPG/C22). There were no significant within- or between-group differences in PROMIS measures or PCDAI. Pre- and post-intervention fecal calprotectin was only available for 4 patients and was excluded from analyses. Secondary outcomes from baseline to week 8 are detailed in Table 2.
Week 16 data were available for 85% of patients and 79% of parents. The significant between-group differences in PedsQL and abdominal pain severity noted from baseline to week 8 were not sustained at week 16, and there were no new significant findings.
Ten of 17 HI patients completing week 8 surveys practiced self-hypnosis consistently, defined as at least 3 to 4 times per week for 8 weeks. The change in Impact III scores from baseline to week 8 was a mean of 13 points greater in those who practiced consistently compared with those who did not (95% confidence interval 1.12, 28.8; P = 0.10; Supplemental Fig. 3, https://links.lww.com/MPG/C23).
HI patients and parents reported a positive experience with CH. In addition to easing abdominal pain, several patients reported benefit for pain from headaches, arthralgias, and injuries. Patients described that CH created an improved sense of control. Several patients used CH to fall asleep and reported improved energy. Patients reported that CH alleviated stress and anxiety, often related to school examinations and performances. Critical feedback included a request for shorter recordings. No adverse effects were reported.
We conducted the first RCT of CH as an adjunct to standard care in pediatric patients with CD. Our findings indicate that CH is acceptable and feasible and may improve pain and psychosocial functioning in adolescents with CD. Parents of patients who underwent CH reported significant improvements in their children's HRQoL, particularly in psychosocial domains, compared with parents of control patients, although changes in patient-reported QoL were not significant between groups. Abdominal pain severity significantly decreased after the CH intervention compared with standard care alone.
We demonstrated high acceptability and feasibility of CH in this patient population. Although the term hypnosis may carry a stigma, our experience was consistent with data showing most people have a positive view of hypnosis and its therapeutic potential (39). Ninety percent of patients approached were interested in trying CH, citing desire for symptom relief, stress reduction, and low risk of harm. Nearly two-thirds enrolled in the study. Approximately half of HI patients ended up practicing self-hypnosis on a regular basis, citing a variety of benefits.
CH may help ease distress provoked by school and social situations, and thus improve QoL. Youth with IBD have reduced QoL and psychosocial impairment even when disease is inactive, in part because of symptoms like fatigue, unpredictable bowel patterns, and altered physical appearance (5,6,40). We found significant improvement in parent-reported QoL in HI compared with WC in social functioning, school functioning, and total score. Although the overall improvements in HI patient-reported QoL scores did not meet statistical significance, patients who practiced self-hypnosis consistently experienced greater self-reported improvement in HRQoL compared those who did not, to an extent that is likely clinically meaningful (29,36,37). Poorer function in WC compared with HI at baseline may have led to an underestimate of post-intervention between-group differences, because QoL in youth with IBD tends to improve over time (37,40). Most patients in our cohort identified school as their primary stressor, with many in homeschool because of their diagnosis, so the improved school functioning and attendance reported by HI parents is clinically meaningful. Feedback demonstrated that parents appreciated the utility of CH and recognized the importance of their children developing coping skills in the face of a lifelong disease, social stressors, and limited pain control options.
Our findings demonstrate that CH may be a useful tool for pain management in CD. Pain in patients with IBD, whether because of active disease, inflammation-mediated changes in nervous system processing, or psychological factors, has few safe and effective remedies (26). Abdominal pain during disease remission, which affected 48% of our cohort, confers risk for depression, anxiety, disability, and reduced QoL (2,41,42). Complaints of pain influence providers’ assessment of disease activity, prompting invasive tests and healthcare costs that may be avoided with better pain management (26). HI patients experienced a significant reduction in abdominal pain severity compared with WC.
The mechanism of action of CH, while not entirely understood, may include neurological, psychosocial, and immune effects. In terms of pain reduction, CH can modulate activity in multiple brain areas involved in sensory processing, including the anterior cingulate, prefrontal and sensory cortices, and insula (13). Psychosocial factors, such as expectancies and motivation are likely relevant (13). Despite substantial improvements in abdominal pain and stool consistency reported by patients with irritable bowel syndrome undergoing CH, studies on the specific effects of CH on gastrointestinal secretions, motility, and visceral sensitivity are inconsistent (43). Preclinical studies demonstrate that psychological stress increases vulnerability to intestinal inflammation, so relaxation induced by CH may be beneficial in IBD (20). Anti-inflammatory effects of CH may occur via vagal nerve stimulation (22,24) and reduction in pro-inflammatory cytokines including interleukin-6 (23) and tumor necrosis factor-alpha (24).
Strengths of our study included the use of an RCT to pilot the novel application of a therapy with known benefits for functional gastrointestinal disorders and psychological distress. We designed CH scripts to target CD symptoms that commonly persist despite usual treatment—abdominal pain, stress, and fatigue. Inclusion criteria were broad to allow generalizability to adolescents with CD. We intentionally designed the intervention as a convenient self-management tool focused on home practice, without adding to the burden of missed work and school, based on studies showing efficacy of CH delivered via audio recordings (44) and skype (45) for FAP.
Our study had a few limitations. The sample size was relatively small; larger studies should be feasible given the considerable patient interest in this therapy. Ninety percent of study patients were recruited during a routine outpatient visit regardless of symptomatology, with 78% in remission, similar to rates at pediatric GI practices nationally (46). Having a relatively healthy baseline sample may explain why improvements were not sustained at week 16; CH may be more impactful in patients with pronounced QoL reductions or active disease. As the same researcher conducted the recruitment, intervention, and data analysis, there was potential for bias, and blinding was precluded. Our study did not allow distinction between specific effects of CH and relaxation or attention. Although Impact III and PedsQL have been shown to correlate (36), our patient and parent survey outcomes differed; this could be in part as youth with IBD may overreport their psychosocial functioning compared with their parents (47). Additional outcome measures, such as clinical interviews to assess psychological comorbidities, may have been helpful. Additional CH sessions and shorter recordings for home practice may have improved compliance. Although CH content was individualized to some extent based on the patient interview, sessions catering to specific needs of a patient, like improved sleep or mood, may have been beneficial. Although adults with IBD have experienced reduced inflammatory markers (48) and improved remission rates (49) with CH, our assessment of disease activity was limited by several factors. We relied on blood and stool tests as ordered by the primary gastroenterologist; for patient convenience, many completed blood tests after the intervention, or on a different day coordinated with their biologic infusions. These values did not reflect a true baseline, as even a single session of CH may alter inflammatory markers (48). Although fecal calprotectin was ordered by the primary gastroenterologist at most visits, only 4/40 patients submitted stool samples both pre- and post-intervention, preventing meaningful analysis. Follow-up was too short to include multiple endoscopic evaluations.
Further research on the role of CH in the biopsychosocial treatment paradigm for youth with IBD is warranted. Future studies may include patients with ulcerative colitis and CD patients with greater symptomatology and compare CH to relaxation and attention. Disease activity should be measured objectively to elucidate the impact of CH on neuroimmune pathways, with biomarkers collected just before study participation to ensure a true baseline. Mucosal and histologic data could be included by enrolling patients at the time of 1 endoscopy and following them until subsequent endoscopy. The use of telemedicine may boost engagement with CH while maintaining accessibility. CH incorporated into CBT protocols may help address unmet mental healthcare needs for these patients (3,4,16). The use of functional neuroimaging, additional biomarkers, and motility studies may shed light on the mechanism of action of CH in patients with IBD.
In summary, CH is a feasible and promising adjunct in a holistic treatment approach for children with CD. Currently, we support the use of CH in patients with IBD when available, especially those suffering from chronic pain and psychosocial dysfunction.
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